Nanoscale Dispensing (NADIS)
In NADIS, a chip that includes a microchannel is employed to deposit small amounts of fluids or droplets on a substrate. The fluid is dispensed manually into a reservoir located in the probe chip, without any external pressure applied to the fluid; only capillary pressure is used to fill the hollow cantilever and to dispense the fluid from the cantilever into the reservoir. However, the probe chip is not coupled with a fluid connection through a special designed probe holder, but is placed on a standard probe holder of a standard AFM instrument.
Patch Clamp Technique:
The Patch clamp technique, described by E. Neher, B. Sakmann and J. H. Steinbach in Pflugers Archiv-European Journal of Physiology 1978, 375, 219 and which is incorporated in herein in its entirety, is used in electrophysiological analysis to study individual ion channels in cell membranes. The patch clamp technique is used to study excitable cells such as neurons, muscle or beta cells of the pancreas. In classical patch clamp technique, the electrode being employed is a hollow glass pipette or a flat surface punctured with tiny holes in so called “planar patch clamp technique”. Both the pipette as well as the tiny holes of the flat surface are filled with a high molar salt solution as a conducting electrode allowing a researcher to keep the voltage constant while observing changes in current. Alternatively, the cell can be “current clamped”, i.e., the current is kept at substantially constant value while changes in membrane potential are observed. The patch clamp technique may only be implemented by highly trained technicians because the pipette is moved by micromanipulators and the position is manually controlled by optical microscopy. The height (z-position) of the pipette is controlled manually only by the focus of the very pipette tip. Consequently, cells are often ruptured, possibly causing the ruptured cells to become not analyzable. This may result in a frustrating, inefficient and time-consuming probing experience, in particular if more than one cell of a network is to be patched.
Microinjection and Patch Clamping Tools
P. K. Hansma et al., disclose in Science 243 (1989) 641, which is incorporated by reference in its entirety, a technique named scanning ion conductance microscopy (SICM). The probe of a microscope employing SICM is an electrolyte-filled micropipette. As the tip of the micropipette approaches a sample, the ion conductance and therefore the current decrease since the gap through which ions can flow, is reduced in size. A feedback mechanism can be used to maintain a predetermined conductance and to determine in turn the distance of the micropipette to the surface of the probe to be sampled. This technique can be employed to spot biotin-modified DNA onto streptavidin-coated and positively charged glass surfaces (cf. to A. Bruckbauer et al. JACS 124 (2002) 8810, which is incorporated herein by reference in its entirety).
Chen et al. disclose in PNAS 104 (2007) 8218, which is incorporated herein in its entirety, a nanoinjector (hereinafter referred to as “nanoneedle”) that employs nanotubes to deliver cargo into cells. A single multiwalled carbon nanotube attached to an AFM tip is adapted to deliver cargo by means of a disulfide-based linker. Depth of penetration of the nanoneedle into cell membranes is controlled by the AFM, whereby the penetration causes a reductive cleavage of the disulfide bonds within the cell's interior, which in turn results in the release of the cargo inside the cells, after the nanoneedle's AFM-controlled retraction from the inside of the cell. The nanoneedle's capabilities were demonstrated by injection of protein-coated quantum dots into live human cells.
Nano Fountain Pen:
Lewis et al. disclose in “Fountain pen nanochemistry: Atomic force control of chrome etching” published in Applied Physics Letters Volume 75, Number 17, 25 October 1999, which is incorporated herein by reference in its entirety, a general method for affecting chemical reactions with a high degree of spatial control that has potentially wide applicability in science and technology. The described technique is based on complexing the delivery of fluids (i.e., liquid or gaseous materials) through a cantilevered micropipette with an atomic force microscope that is totally integrated into a conventional optical microscope. Controlled etching of chrome is demonstrated without detectable effects on the underlying glass substrate. This simple combination allows for the nanometric spatial control of the whole world of chemical reactions in defined regions of surfaces. Applications of the technique in critical areas such as mask repair are likely.
Tapered Microcapillaries:
Several groups developed dispensing techniques using tapered microcapillaries. The motion with respect to the surface of such probes is controlled optically or by a shear-force feedback control using a dither PZT piezo. But all these techniques suffer from the absence of a real force sensor that measures the normal force exerted on the sample. Furthermore, all this probes have only circular apertures located at the very end of the tapered microcapillaries
U.S. Pat. No. 6,353,219, which is incorporated herein by reference in its entirety, discloses an object inspection and/or modification system and method. It is concerned with a SPM (scanning probe microscopy) system for modifying an object that includes producing measurements indicative of modifications to be made to the object. The object may be a biological cell or material. In accordance with the measurements, one or more SPM probes are manipulated to effect the modifications. The device includes a fluid material delivery tool having a cantilever with a tapered tip and a capillary in the core material of the tip. The capillary is connected to a duct in the cantilever arm and the duct is connected to a pumping chamber.
U.S. Pat. No. 7,045,780, which is incorporated herein by reference in its entirety, discloses a scanning probe microscopy inspection and modification system. It is concerned with a microstructured SPM (scanning probe micicroscopy) probe for use in inspecting an object by making SPM measurements of the object, such as AFM (atomic force microscopy), STM (scanning tunnelling microscopy) and other techniques. The probe has several cantilevers, each connected to a tip activation control circuit.
It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate identical or analogous elements but may not be referenced in the description for all figures.